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Stem Cell Transplantation
Stem Cell Transplantation
Stem cell transplantation (SCT) is widely used to treat haematological malignancies such as
lymphomas, multiple myeloma and myeloid/lymphoblastoid leukaemias. It is potentially
applicable as a treatment for some solid organ tumours such as breast cancer and renal cell
carcinoma, and is increasingly used to treat non-malignant conditions. The principle is to ablate the
Due to the non-myeloablative nature of the reduced intensity conditioning, following infusion there is
a period of mixed-chimerism with both patient and donor cells present. The donor cells should
eventually out-compete, leading to the immune system becoming fully donor (Figure 1).
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CATEGORY: ORGANS & TISSUES STEM CELL TRANSPLANTATION
Stem Cell
Transplantation
cont.
Donors are selected on the basis of HLA-compatibility. The more closely matched the donor and
recipient are, the less risk of potentially life-threatening graft-versus-host disease (GvHD) where
the new donor immune cells attack recipient tissues, often skin, gut and liver (Figure 2). This can
be very debilitating or even fatal.
An important effect following SCT is graft-versus-leukaemia (GvL), which is essential to prevent
relapse when treating malignant disease. Both of these effects are thought to be mainly T-cell
mediated and GvHD incidence is associated with decreased risk of relapse. Studies have shown
that one group of important GvL targets are haematopoietically expressed minor
histocompatibility antigens (mHAgs), such as HA-1. However it has also been observed that
there are GvL reactions following syngeneic transplantation which are unlikely to be caused by
mHAg mis-matches, suggesting that GvL could also have a tumour-specific component. This could
potentially be directed against tumour-specific antigens such as the cancer-testis antigen (CTAg)
family of tumour proteins, or antigens such as PRAME which can be overexpressed by tumours.
Although cancer patients may develop tolerance to tumour-associated antigens, SCT can facilitate
development of effective immune responses as the donor system is unlikely to have become
tolerised to these cancer proteins.
Occurrence of GvHD presents problems, but has been linked to a decrease in relapse risk,
probably due to GvL. Consequently, there is much research interest in trying to enhance the GvL
effect whilst simultaneously reducing GvHD.
http://www.cmaj.ca/cgi/content-nw/full/170/10/1569/F432